Microstructured Discrimination Device

ABSTRACT

The present invention discloses a microstructured discrimination device for separating hydrophobic-hydrophilic fluidic composites comprising particulate and/or fluids in a fluid flow. The discrimination is the result of surface energy gradients obtained by physically varying a textured surface and/or by varying surface chemical properties, both of which are spatially graded. Such surfaces discriminate and spatially separate particulate and/or fluids without external energy input. The device of the present invention comprises a platform having bifurcating microchannels arranged radially. The lumenal surfaces of the microchannels may have a surface energy gradient created by varying the periodicity of hierarchically arranged microstructures along a dimension. The surface energy gradient is varied in two regions. In one pre-bifurcation region the surface energy gradient generates a fluid flow. In the other post-bifurcation region, there is a difference in surface energy proximal to the bifurcation such that different flow fractions are divided into separate channels in response to different surface energy gradients in each of the post-bifurcation channels. Accordingly, fluids of different hydrophobicity and/or particulate of different hydrophobicity are driven into separate channels by a global minimization of the fluid system energy.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims benefit of the following patent application(s)which is/are hereby incorporated by reference: U.S. patent applicationSer. No. 16/690,666 filed on Nov. 21, 2019, and U.S. Provisional PatentApplication No. 62/770,565 filed on Nov. 21, 2018.

A portion of the disclosure of this patent document contains materialthat is subject to copyright protection. The copyright owner has noobjection to the reproduction of the patent document or the patentdisclosure, as it appears in the U.S. Patent and Trademark Office patentfile or records, but otherwise reserves all copyright rights whatsoever.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

REFERENCE TO SEQUENCE LISTING OR COMPUTER PROGRAM LISTING APPENDIX

Not Applicable

BACKGROUND SUMMARY

The present invention relates generally to a device comprising spatiallyvarying hierarchical microstructures.

More particularly, this invention pertains to a device comprisingspatially varying hierarchical microstructures to generate graded Wenzeland graded Cassie interfaces with fluid flow. These graded interfacesmay be characterized by surface energy gradients. These surface energygradients may involve separately, or in combination, spatially varyingmicrostructures to generate a spatially varying chemically inducedsurface energy gradient that may drive fluid flow in a device.

The behavior of fluids at the scale of microns and smaller can differfrom “macrofluidic” behavior in that factors such as surface tension,energy dissipation, and fluidic resistance start to dominate the systemdynamics. At small scales (channel size and surface textures of around100 nanometers to 500 micrometers) some interesting and sometimesunintuitive properties appear. In particular, the Reynolds number (whichcompares the effect of the momentum of a fluid to the effect ofviscosity) can become very low. A key consequence is composite fluidstransition to a co-flowing fluid state, wherein the fluid constituentsdo not necessarily mix in the traditional sense. As flow becomes laminarrather than turbulent, molecular transport between the co-flowing fluidsmust often be through diffusion. It is also noted that ion exchangesurfaces can generate very high osmotic pressures of over 100 MPa inwater because they create high surface concentrations of counter-ions.Poly-ionic nanoparticles, with high surface area, produce such a greatosmotic pressure that they can be used in practical desalinationprocesses. Counter-ions and solutes present difficulties when trying tounderstand and develop microfluidic systems, thus a system that isuncharged without the presence of counter-ions or solutes but has thesame characteristics would be beneficial.

Microfluidics-based devices, capable of continuous sampling andreal-time testing of fluid samples for biochemical toxins and otherdangerous pathogens, can serve as an always-on early warning system forbiothreats.

In open microfluidics, at least one boundary of the system is removed,exposing the fluid to air or another interface (i.e., liquid).Advantages of open microfluidic systems include accessibility to theflowing liquid for intervention, larger liquid-gas surface area, andminimized bubble formation.

Another advantage of open microfluidics is the ability to integrate opensystems with surface-tension driven fluid flow architectures. Surfacetension driven fluid flow eliminates the need for external pumpingmethods such as peristaltic or syringe pumps.

Open microfluidic devices are also easy and inexpensive to fabricate bymilling, thermoforming, and hot embossing. In addition, openmicrofluidics eliminates the need to glue or bond a cover for deviceswhich could be detrimental for capillary flows. Examples of openmicrofluidics include open-channel microfluidics, rail-basedmicrofluidics, paper-based, and thread-based microfluidics.Disadvantages to open systems include susceptibility to evaporation,contamination, and limited flow rate.

In continuous-flow microfluidics, manipulation of continuous liquid flowis achieved through microfabricated channels. Actuation of liquid flowis implemented either by external pressure sources, external mechanicalpumps, integrated mechanical micropumps, or by combinations of capillaryforces and electrokinetic mechanisms. Continuous-flow microfluidicoperation is the mainstream approach because it is easy to implement andless sensitive to protein fouling problems. Continuous-flow devices areadequate for many well-defined and simple biochemical applications, andfor certain tasks such as chemical separation, but they are lesssuitable for tasks requiring a high degree of flexibility or fluidmanipulations. These closed-channel systems are inherently difficult tointegrate and scale because the parameters that govern flow field varyalong the flow path making the fluid flow at any one location dependenton the properties of the entire system.

In droplet-based microfluidics, manipulation of discrete volumes offluids is performed in immiscible phases with low Reynolds number andlaminar flow regimes. Interest in droplet-based microfluidics systemshas been growing substantially in past decades. Microdroplets allow forhandling miniature volumes (μl to fl) of fluids conveniently, providebetter mixing, encapsulation, sorting, and sensing, and suit highthroughput experiments. Exploiting the benefits of droplet-basedmicrofluidics efficiently requires a deep understanding of dropletgeneration to perform various logical operations such as droplet motion,droplet sorting, droplet merging, and droplet breakup. Microstructuredsurfaces are particularly useful in manipulating and forming specializedinterfaces with droplets in a microfluidic setting.

In digital microfluidics, discrete, independently controllable dropletsare manipulated on a microstructured substrate using electrowetting.Following the analogy of digital microelectronics, this approach isreferred to as digital microfluidics. Electrocapillary forces are usedto move droplets on a digital track. In digital microfluidics there is anotion of a “fluid transistor”. By using discrete unit-volume droplets,a microfluidic function can be reduced to a set of repeated iterativeoperations, i.e., moving one unit of fluid over one unit of distance.This “digitization” method facilitates the use of a hierarchical surfacestructure approach for microfluidic biochip design. Digitalmicrofluidics offers a flexible and scalable system architecture as wellas high fault-tolerance capability. The electrowetting mechanism allowseach droplet to be controlled independently, and enables the wholesystem to be dynamically reconfigured, whereby groups of hierarchicaldomains in a microfluidic array can be reconfigured to change theirfunctionality during the concurrent execution of a set of bioassays. Onecommon actuation method for digital microfluidics iselectrowetting-on-dielectric (EWOD). However, surface acoustic waves,optoelectrowetting, mechanical actuation, etc., are also methods ofdigitally manipulating fluid droplets.

In paper-based microfluidics, devices comprise surface microstructurehydrophobic barriers on hydrophilic paper that passively transportaqueous solutions to outlets where biological reactions take place.Current applications include portable glucose detection andenvironmental testing, with hopes of reaching areas that lack advancedmedical diagnostic tools.

Microfluidics may also be combined with landscape ecology, either in thein vitro or in vivo environment. A nano/micro-structured fluidiclandscape can be constructed by juxtaposing local patches of surfacemicrostructure intended to create a bacterial and/or cellular habitatand connecting different microstructures patches by dispersal corridorsto create a landscape. The resulting landscapes can be used as physicalimplementations of an adaptive landscape, by generating a spatial mosaicof patches of biological opportunity distributed in space and time. Thepatchy nature of these fluidic landscapes allows for the study ofadapting bacterial and body cells in a metapopulation system.Microstructured landscapes can be used to study the evolutionary ecologyof bacterial and cellular systems in a synthetic ecosystem setting. Inan implant situation, microstructured landscapes can direct complex,organized tissue structures to improve healing or drive regeneration ofan organ.

For example, microstructured landscapes can drive precise and carefullycontrolled chemoattractant gradients by using microfluidics. Controlledchemoattractant microstructured landscapes can be used to control cellmotility and chemotaxis. Conversely, microstructured landscapes can beused to study the evolution of bacterial resistance to antibiotics insmall populations of microorganisms and in a short period of time. Thesemicroorganisms including bacteria and the broad range of organisms thatform the marine microbial loop, responsible for regulating much of oceanbiogeochemistry. Microstructured landscapes have also greatly aided thestudy of durotaxis by facilitating the creation of durotactic(stiffness) gradients.

Thus, what is needed then is a device with microstructured surfaces thatcan discriminate between various fluid components and is applicable to avariety of microfluidic systems.

BRIEF SUMMARY

In some embodiments, a fluid separating device is disclosed which mayinclude a base that may comprise a directing channel having a first endand a second end. The second end of the directing channel may beconnected to a first and a second separation channel, the first andsecond separation channels diverging from the second end of thedirecting channel. The directing channel may also include a surface thatcomprises a first hierarchical microstructure configured to direct flowof a fluid from the first end to the second end. The first separationchannel may include a surface comprising a second hierarchicalmicrostructure configured to selectively direct flow of at least aportion of the fluid from the directing channel to the first separationchannel. The second separation channel may include a surface comprisinga third hierarchical microstructure configured to selectively directflow of at least a portion of the fluid from the directing channel tothe second separation channel.

In some embodiments, the fluid separating device may further include aninjection port disposed on the base wherein the injection port may beconnected to the first end of the directing channel.

In some embodiments, the fluid separating device may include the secondhierarchical microstructure of the first separation channel forming agraded Wenzel state and the third hierarchical microstructure of thesecond separation channel forming a graded Cassie state.

In some embodiments, the second and third hierarchical microstructuresmay each comprise distinct surface energy gradients.

In some embodiments, the distinct surface energy gradients may be formedby spatially varying the spatial periodicity of the second hierarchicalmicrostructures in relation to the third hierarchical microstructures.

In some embodiments, the fluid may include at least a first componentand a second component, the distinct surface energy gradients of eachsecond and third hierarchical microstructures may be configured toseparate the first component and the second component into distinctflows.

In some embodiments, the first component's distinct flow may be directedto the first separation channel and the second component's distinct flowmay be directed to the second separation channel.

In some embodiments, each of the first, second, and third hierarchicalmicrostructures may be formed of spatially varying microstructurecomponents, wherein the spatially varying components may be arranged ina hierarchy and include variations in height and diameter between 10nanometers and 1000 microns. Additionally, each of the first, second,and third hierarchical microstructures may be formed of spatially varymicrostructures components, wherein the spatially varying microstructurecomponents may be arranged adjacent to each other having a pitch ofbetween 10 nanometers and 1000 microns.

In some embodiments, the first component flow may include a first solidand the second component flow may include a second solid, the firstsolid may be different from the second solid.

In some embodiments, the first solid may include red blood cells and thesecond solid may include platelets.

In some embodiments, the first component flow may include a solid andthe second component may include the absence of said solid.

In some embodiments, the first component may include red blood cells andplatelets and the second component may include blood serum.

In some embodiments, the fluid separating device may further include atleast one collection reservoir that is communicated with the first orsecond separation channel.

In some embodiments, a fluid separating device may comprise a base whichmay include a directing channel having a first end and a second end. Thesecond end may be connected to a first and a second separation channel.The first and second separation channels may diverge from the second endof the directing channel. The directing channel may include a surfacecomprising a first hierarchical microstructure configured to direct flowof a fluid from the first end to the second end. The first separationchannel may include a surface comprising a second hierarchicalmicrostructure configured to selectively direct flow of at least aportion of the fluid from the directing channel to the first separationchannel. The second separation channel may include a surface comprisinga third hierarchical microstructure configured to selectively directflow of at least a portion of the fluid from the directing channel tothe second separation channel. The second separation channel may furtherdiverge with a first output being in fluid communication with a returnline and a second output being in fluid communication with a collectionreservoir.

In some embodiments, the fluid separating device may further include aninput reservoir for supplying a fluid.

In some embodiments, the fluid separating device may further include aninput port configured to receive fluid from the input reservoir anddirect the fluid to the directing channel.

In some embodiments, the return line may be in fluid communication withthe input reservoir.

In some embodiments, the fluid separating may further comprise a fluidmonitor disposed upstream of the collection reservoir such that thefluid monitor may be configured to measure fluid conductivity.

To enable the objectives, technical contents, characteristics andaccomplishments of the present invention to be more easily understood,the embodiments of the present invention are described in detail incooperation with the attached drawings below.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a diagram schematically illustrating a generalizedmicrostructured fluid discrimination device of the present invention.

FIG. 2 is a diagram schematically showing the microstructured fluiddiscrimination device according to one embodiment of the presentinvention.

FIG. 3 is a diagram schematically showing the microstructured fluiddiscrimination device according to another embodiment of the presentinvention.

FIG. 4 is a diagram of a Y-discriminator illustrating the mechanism ofcomponent fluid separation.

FIG. 5A is an illustration of one embodiment of hierarchicalmicrostructured gradient patterns for directing channel according to thepresent invention.

FIG. 5B is an illustration of one embodiment of a hierarchicalmicrostructured pattern having a sinusoidal waveform for directingchannel according to the present invention.

FIG. 5C is an illustration of another embodiment of hierarchicalmicrostructured gradient patterns for directing channel according to thepresent invention.

FIG. 6 is a diagram of a hierarchical microstructured gradient patternfor a separating channel according to the present invention.

FIG. 7 is a diagram of the internal microstructure of a separatingchannel of a microstructure discriminator for separating red blood cellsfrom whole blood according to the present invention.

FIG. 8 is a diagram of the internal microstructure of a separatingchannel of a digital microstructured fluid discrimination deviceaccording to the present invention.

FIG. 9 is a diagram of the internal microstructure of a evolutionchamber in a landscape microstructured fluid discrimination device forstudying cell-surface interactions according to the present invention.

FIG. 10 is a first embodiment of a fan discriminator for separating redblood cells from whole blood according to the present invention.

DETAILED DESCRIPTION

The following detailed description and appended drawings describe andillustrate various exemplary embodiments of the invention. Thedescription and drawings serve to enable one skilled in the art to makeand use the invention. Although the present invention will be describedwith reference to preferred embodiments, those skilled in the art willrecognize that changes may be made in form and detail without departingfrom the spirit and scope of the invention. As such, it is intended thatthe following detailed description be regarded as illustrative ratherthan limiting and that it is the appended claims, including allequivalents thereof, which are intended to define the scope of theinvention.

In the present application, the terms “comprise(s),” “include(s),”“having,” “has,” “contain(s),” and variants thereof, are intended to beopen-ended transitional phrases, terms, or words that do not precludethe possibility of additional acts or structure.

As used herein, the terms “surface energy” and “interfacial free energy”refer to the free energy due to disruption of intermolecular bonds thatoccur when a surface is created. The physics of materials requires thatsolid surfaces be intrinsically less energetically favorable than thebulk of a material (the molecules on the surface have more energycompared with the molecules in the bulk of the material), otherwisethere would be a driving force for surfaces to be created, and theremoval of bulk material. Removal of bulk material occurs in substancesthat dissolve from the inside out, and these substances have negativesurface energy. Positive surface energy may therefore be defined as theexcess energy at the surface of a material compared to the bulk, or itis the work required to build an area of a particular surface. Anotherway to view the surface energy is to relate surface energy to the workrequired to cut a bulk sample, creating two surfaces.

As used herein, the terms “surface energy gradient” and “interfacialfree energy gradient” refer to a surface on which the surface energyvaries as a function of distance along the surface. The gradient is thechange in surface energy over a unit distance. Generally, the unitdistance is sufficiently small such that the surface energy is linearlyincreasing or linearly decreasing over the chosen spatial interval.

As used herein, the term “wetting” is an interfacial term describing thestate of a drop of liquid on a solid substrate. If the interfacialenergy decreases then the spreading parameter S increases. The spreadingparameter can be used to mathematically determine this: where S is thespreading parameter, the surface energy of the substrate, the surfaceenergy of the liquid, and the interfacial energy between the substrateand the liquid.

-   -   If S<0, the liquid partially wets the substrate.    -   If S>0, the liquid completely wets the substrate.

As used herein, the terms “hydrophobic” and “hydrophilic” refer to arelative relation between surfaces A and B. A is hydrophobic relative toB if SA<SB, where SA is the spreading parameter of surface A and SB isthe spreading parameter of surface B, and the drop used is water.Conversely, B is hydrophilic relative to A.

As used herein, the terms “lipophobic” and “lipophilic” refer to arelative relation between surfaces A and B. A is lipophobic relative toB if SA<SB, where SA is the spreading parameter of surface A and SB isthe spreading parameter of surface B, and the drop used is a lipid.Conversely, B is lipophilic relative to A. These terms may also dependon what kind of lipid drop used in the measurement.

As used herein, the term “microstructure” refers to any surface textureor surface treatment which may be comprised of a plurality of surfaceelements or features that have a spatial dimension between 100 nanometerand 10,000 microns.

As used herein, the term “hierarchical microstructure” refers to anysurface texture comprising multiple surface elements or features thatcan be grouped by a characteristic spatial dimension in some range. Eachof these groupings is called a hierarchical level. The dimensionalranges may overlap, but the mean value in each group should be distinct.Therefore, one can speak of one hierarchical level being larger thananother hierarchical level if the mean of the dimensional range of oneis larger than the mean of the dimensional range of the other. Ahierarchical microstructure has at least one smaller hierarchical levelposition on top of at least one larger hierarchical level. For example,small diameter cylinders positioned on the terminal surface of a largerdiameter cylinder. The microstructure may comprise surface treatments inaddition to surface textures. For example, small diameter hydrophobiccircular coatings may be positioned on the terminal surface of a largerdiameter cylinder. The microstructure may be comprised only of stackedsurface treatments.

As used herein, the term “surface treatment” can refer to a coatingsubstance with a surface energy different from the substrate on which itis placed. Alternatively, a surface treatment may be any treatment thatlocally alters the surface energy of a substrate or feature.

As used herein, the term “surface feature” (may also be referred to as“surface element”) can refer to a geometrical object projecting out fromor into a substrate surface. The surface feature comprises either theaddition or removal of the substrate material. When the substratematerial spatially varies, then surface features comprise either thelocal addition or removal of the substrate material. Spatially varyingsurface features may comprise surface features with differ in surfaceenergy relative to the local surface energy of the substrate. Spatiallyvarying surface features differ from surface treatments in that surfacefeatures have a three-dimensional form. It will also be understood thatthe addition of material may comprise material different than thesubstrate material, for example, but not limited to, the addition of apolymer, alloy, metal, plastic, composite, or the like.

As used herein, the term “complex fluid” (also referred to as “compoundfluid”) refer to a fluid comprised of two or more gaseous, liquid,and/or solid substances. A substance can be atoms, molecules,particulate, or life forms. For example, whole blood may be considered acomplex fluid for the purposes of this disclosure, comprising multipleliquid and/or solid substances. Similarly, a mixture of oil and vinegarmay be considered a complex fluid for the purposes of this disclosure.

As used herein, the term “separating microstructure” refers to anymicrostructure that discriminates between substances by the interfacialsurface energy they generate with the surfaces. When combined with achannel, a separating microstructure may attract some substances andrepels others. If the separating microstructure is digital, then it mayattract a substance in one state and repel the same substance in anotherstate. An example may include electrowetting for the purposes of thisdisclosure.

As used herein, the term “directing microstructure” refers to anymicrostructure that promotes fluid flow in a predetermined direction. Ifthe directing microstructure is digital, then it may promote fluid flowin a multiplicity of predetermined directions.

As used herein, the term “electrowetting” refers to the modification ofthe wetting properties of a surface (which is typicallyhydrophobic/lipophilic) with an applied electric field.

As used herein, the term “Wenzel state” refers to an interfacial statebetween two phases of matter, wherein the surfaces of the two phases atthe point of contact generate a low contact angle. A Wenzel state isusually considered to be a wetting state.

As used herein, the term “Cassie state” and “Cassie-Baxter” refers to aninterfacial state between two phases of matter, wherein the surfaces ofthe two phases at the point of contact generate a high contact angle. ACassie state is usually considered to be a non-wetting state.

As used herein, the term “Wenzel-Cassie state” refers to an interfacialstate with a heterogeneous surface. Unlike Wenzel and Cassie stateswhich are point-wise defined, the Wenzel-Cassie state refers to a regionon a surface between two phases of matter, wherein the surfaces of thetwo phases at the point of contact generate a low contact angle in someregions and a high contact angle in other regions. Generally, the Wenzeland Cassie regions are juxtaposed, and arranged such that one phase ispinned or localized with respect to the other phase. The localization isdue to the fact that the Wenzel-Cassie state is a lower energy statecompared to breaking the Wenzel-Cassie state. For translation betweenthe two phases to occur, energy must be supplied to break theWenzel-Cassie state.

As used herein, the term “graded Wenzel state” refers to an interfacialstate between two phases of matter, wherein the surfaces of the twophases at the point of contact generate a low contact angle, and thatcontact angle varies as one phase is translated with respect to theother.

As used herein, the term “graded Cassie state” refers to an interfacialstate between two phases of matter, wherein the surfaces of the twophases at the point of contact generate a high contact angle, and thatcontact angle varies as one phase is translated with respect to theother.

As used herein, the term “graded Wenzel-Cassie state” refers to aninterfacial state with a heterogeneous surface. Unlike Wenzel and Cassiestates which are point-wise defined, the Wenzel-Cassie state refers to aregion on a surface between two phases of matter, wherein the surfacesof the two phases at the point of contact generate a low contact anglein some regions and a high contact angle in other regions. Generally,the Wenzel and Cassie regions are juxtaposed, and arranged such that onephase is pinned or localized with respect to the other phase. Thelocalization is due to the fact that the Wenzel-Cassie state is a lowerenergy state compared to breaking the Wenzel-Cassie state. Fortranslation between the two phases to occur, energy must be suppliedthat exceeds the energy barrier, and to break the Wenzel-Cassie state. Agraded Wenzel-Cassie state is an interfacial state in which the energybarrier varies as one phase is translated with respect to another.

As used herein, the term “component flow” refers to one of at least twoflows derived from a first complex fluidic flow, wherein each derivedcomponent flow can be spatially separated from the other componentflows. When separated, component flows may be compositionally distinct,although the two flows may share some constituents.

As used herein, the term “microstructured water” refers to interfacialwater next to a high surface energy surface. The high surface energycreated by a hierarchical microstructure organizes water and expelssolute at the interface to the bulk of the solution. The region ofinterfacial microstructure water may be several hundred microns inwidth.

As used herein, the term “phase” refers to a relative designationregarding surface energy. For example, a three-phase system of solidpolymer, water and air comprises three phases of different surfaceenergy. However, a three-phase system need not be comprised of a solid,liquid and gas. For example, a three-phase system may be comprised of asolid, water, and a liquid lipid.

As used herein, the term “carrier phase” refers to the arrangement ofphases in a three-phase system. For example, in a three-phase systemcomprising solid, water and air, the interfacial geometry is describedby a sphere of water in contact with a polymer plane surface surroundedby air. The surrounding phase is the carrier phase. In the example ofthe solid-water-lipid system, if the solid has a low surface energy(hydrophobic), then the lipid forms the droplet on the polymer surfaceand water becomes the carrier. Conversely, if the solid has high surfaceenergy, then water forms the drop in association with the polymer andthe lipid becomes the carrier phase.

It should be understood that the terms hydrophilic and hydrophobic aresystem-specific, and the interfacial geometries (Wenzel or Cassie) arealso system specific. Indeed, the Wenzel-Cassie state is the onlyinterfacial state that has a system independent status, provided thesystem comprises at least three phases. Clearly which phase forms theWenzel interface and which forms the Cassie interface is still systemspecific, but for a surface texture that forms a Wenzel-Cassie interfacefor a given three-phase system will generally form a Wenzel-Cassieinterface for any three-phase system.

The present disclosure describes a device with microstructured surfacetextures which create a surface energy gradient that may be fabricatedfrom physical or chemical methods. A device which has interfacial waternext to a high surface energy surface, the high surface energy createdby a hierarchical microstructure, organizes water and expels solutes atthe interface to the bulk of the solution. This expulsion creates anexclusion zone ranging several hundred microns. These exclusion zonesmay be found in the vicinity of microstructured surfaces usinglow-molecular weight dyes, protein solutions, and solutions comprisingmicron-sized microspheres.

The exclusion zone may exhibit interesting properties. For example, acalculation using a para-ortho model of water suggests the exclusionzone may have enhanced absorption in the short UV light range. Indeed,UV light may spatially expand the exclusion zone and reduce the entropyof water and order the structure of the water in exclusion zones.

Unexpectedly, in a para-ortho model of water interacting with amicrostructured surface, calculations may indicate that microstructuredsurfaces of the present disclosure can generate in some cases a surfaceenergy gradient sufficient to cause water to seek a lower energy statein which the density of the microstructured water is higher than waternot in a microstructured state. Because the water is microstructured,its viscosity may be higher. This effect may create, in practice,Wenzel-Cassie zones of microsurface-target-surface interfaces that areinterlocking.

It is therefore useful to summarize these findings in order to provide acontext for the present disclosure. In some embodiments, wherever wateris present in solution with respect to a microstructured surface, thewater may be considered as being either ‘bound’ or ‘free’, correspondingto whether the surface in interaction possesses high or low surfaceenergy, respectively. In words more familiar to those in the biologicaldisciplines, the surfaces may be hydrophilic or hydrophobic,respectively. By structuring the free state of water by forming adjacentbound states, one can realize virtual size exclusion filters useful inthe separation of components of complex (compound) fluids.

The relation between water as a pure molecule and any other moiety maybe considered a bound state when the combination of water and the moietyis a lower entropy state compared with pure molecular water. Low entropywater is another description of microstructured water.

Microstructured water may be considered a solute and not part of thedissolving free water. Thus, in generating regions of free waterjuxtaposed by regions of microstructured water, one may create regionsof mostly hydrogen bonded structures surrounded by higher density waterconsisting of much smaller, less extensive clusters.

Hierarchically microstructured surfaces may induce spatial regions ofstrongly and weakly hydrogen bonded water molecules, which in turn mayinduce differences with respect to their water activity and chemicalpotential. Normally, any such spatially discontinuous interfaces inwater activity and chemical potential between different regions withinthe same mass of liquid could rapidly cause liquid movement from one tothe other in order to equalize these states and so remove the chemicalpotential differences. However, where there are hierarchicallymicrostructured surfaces interacting with the aqueous solution, theconcentration of the more extensive hydrogen-bonded clusters associatedwith certain surface textures may form a layer of water with propertiesdiffering from the bulk values. The surface interactions may prevent thepotential equalization between bulk and surface volumes, thus generatinggradients in energy. When this occurs, the interfacial water may have adifferent energetic state and chemical potential compared with water inthe bulk, which may lead to differences in potential energy.

Recognizing that the notion of the hydrophilicity of a surface isrelative to adjacent surfaces, interactions between the surface andneighboring water molecules may fix the localized hydrogen bonding andthis, together with steric factors, may increase the cluster extent andhalf-life of these clusters. The longer life of these structures maylead to more extensive hydrogen bonded clusters, so the energy gradientmay increase. This increase in energy gradient next to the texturedsurface may displace solutes from the region next to the surface towardsthe bulk water until a balance is reached between entropic and energeticconsiderations.

The effect of this non-water expulsion, be the expelled matterparticulate or a different molecule, may be the formation of anincreased concentration band of solute as expelled material mixes withthe bulk solution concentration. If two hierarchically structuredsurfaces define the boundaries of a region, then the excluded materialmay tend to concentrate at the center of the boundary-defined region.The type of matter that is excluded depends on the structure of themicrostructured surfaces and the hydrophilicity of the waterconstituents.

For example, consider a solution of suspended hydrophilic microparticlesor nanoparticles. The surfaces of these particles may cause mutuallyrepulsive osmotic pressure effects that may result in the ordering ofthe particles within small volumes of the liquid. Hence, the effectdescribed here is an osmotic potential that may not require a membrane.The condition may be considered as a virtual filter. Indeed, any twosubstance may be separated provided they form a solution, and the twosolutions are of different hydrophilicity, or two phases.

These microstructure domains may possess properties similar to thephenomenon known as autothixotropy. Therefore, the fluid dynamics nearhierarchically microstructured surfaces may be considered non-Newtonian.In particular, microstructured domains as disclosed herein generallytend to increase in viscosity as a function of time.

Since hydrogen bonding is strongly influenced by the delocalization ofelectrons, it may be expected that the application of a magnetic field,electric field, or electrostatic potential would extend the waterclustering.

Another effect of the hierarchically microstructured surfaces of thepresent disclosure is the formation of evanescent waves due to theinternal reflection of electromagnetic radiation. The standingelectromagnetic wave produced by internal reflection may interact withwater molecules to stabilize a standing wave of hydrogen bonded clustersthat can increase the local concentration and extent of hydrogen bondedclusters and consequently increase the above osmotic effect.

The effects reported here are not limited to water but may occur for avariety of polar solvents that can form hydrogen bonds. This disclosuremay further describe a mechanism that does not depend on the specificcolligative thermodynamic properties of water.

It is often overlooked that fluid water may actually be a complex orcomposite fluid comprised of two distinct nuclear-spin isomers, para-and ortho-water, which may not interconvert in isolated molecules. Muchlike water and oil form discrete hydrophilic and hydrophobic phasedomains in the presence of a gravitational gradient, so too para- andortho-water may form discrete domains, provided there is a surfaceenergy gradient present. Differences in hydrophobicity andhydrophilicity at spatially separate locations on a solid substrate maygenerate an energy gradient when these surfaces are in contact with anaqueous solution.

Another way to understand the effects disclosed herein generically comeunder the term “surface tension”. Surface tension may be understood aslinearly related to spatial dimension, hence, the smaller the system,the greater the influence of surface tension. A system ofmicrostructured features, termed herein as a hierarchicalmicrostructured surface, may for interfacial domains with liquids whichcan be dominated by surface tension effects.

Parameters that affect surface tension and can control a microstructureddiscriminator may include thermal energy (thermocapillary effect) andelectric energy (electrowetting effect). Microstructured discriminatorsof the present disclosure may utilize thermal energy and electric energyto locally change the surface tension of fluids and then change thefluid-microsurface interface composition and geometry.

While the present disclosure describes an innovation in microsurfacetechnology, it should be appreciated that the disclosures made hereinare readily adapted to microfluidic technology. Advances inmicrofluidics technology are revolutionizing molecular biologyprocedures for enzymatic analysis (e.g., glucose and lactate assays),DNA analysis (e.g., polymerase chain reaction and high-throughputsequencing), and proteomics. The basic idea of microfluidic biochips isto integrate assay operations such as discrimination, as well as samplepre-treatment and sample preparation on one chip.

Referring now to FIG. 1 , a microstructured discriminator of the presentdisclosure is illustrated. As shown in FIG. 1 , the microstructureddiscriminator 100 may include an injection port 102 and multipledirecting channels 104 which may radiate outward from the injection port102. The injection port 102 and directing channels 104 may be disposedon the surface 106 of the microstructured discriminator 100. Eachdirecting channel 104 may be associated with two separating channels oftype 108 and type 110. Fluid 112 may be supplied to injection port 102and may be comprised of at least three fluid types. Fluid type A 114 maybe a neutral carrier fluid, typically water in some embodiments. Fluidtype B 116 may be attracted to channel type 108 and fluid type C 118 maybe attracted to channel type 110. It should be understood that the term“fluid type” does not necessarily indicate a fluid. In some embodiments,a neutral fluid type 114 may be serum, fluid type 116 may be red bloodcells, and fluid type 118 may be all other blood constituents, e.g.,platelets. Accordingly, in some embodiments, the microstructurediscriminator 100 can be a device for separating red blood cells fromwhole blood. The bifurcating network comprising directing channels 104and separating channels 108 and 110 may terminate in collection channels120 and 122. Collection channel 120 may consolidate fluid type 116 andcollection channel 122 may consolidate fluid type 118. The collectionchannels may terminate in collection reservoirs 124 and 126.

In some embodiments, a microstructured fluidic separating andconsolidation device may include a surface energy gradient residing inthe directing and separating channels and may be used to direct andseparate fluidic constituents based on their hydrophobic/lipophobiccharacteristics. The microstructures of the channel surfaces may developinterface phenomena between the fluid constituents and the surfaces ofthe channels so that the composite fluid comprising different fluidtypes may be directed to move and separate into diffluences.

In some embodiments, a microstructured fluid discrimination andconsolidation device may include capillary force driving means to drivethe composite fluid through the discriminator causing fluid constituentsto separate, successively concentrate, and then terminally consolidateinto collection reservoirs. Static surface energy gradients can beformed by varying the diameter, pitch, height, bulk material, shape, andnumber of hierarchical levels, and the relations between hierarchicallevels. Some hierarchical structures generate capillary forces, otherscreate Wenzel-Cassie domains. Hierarchical microstructures can comprisemicropatterns on different size scales, preferably one on top ofanother, wherein their hydrophobicity or lipophobicity may be determinedby the surface patterns in some cases and by the chemistry of the bulkmaterial in other cases.

The underlying principle is to use bulk chemistry and surfacemicrostructure to create different surface tension gradients betweencomposite fluids and the inner walls of the directing and separatingchannels. In particular, the microstructure of the directing surfacesmay cause composite fluid flow in a particular direction withoutexternal means, i.e., using micro pumps.

In some embodiments, the composite fluid may flow to the bifurcationregions located at the junction of the directing channel and theseparating channels, where microstructures on the internal surfaces mayspontaneously separate components fluids from the composite fluid byutilizing different surface tension gradients in the separatingchannels. The term “density-variation” is intended to mean any variationin diameter, pitch, height, bulk material, shape, and number ofhierarchical levels, and the relations between hierarchical levels thatcreate a surface energy gradient.

The bifurcation regions may connect the directing channels with theseparation channels. The separation channels may have differentinterfacial surface energy. In some embodiments, a complex fluid mayflow to the bifurcation region where the complex fluid separates intocomponent fluids which may enter separate channels corresponding tominimal interfacial surface energy for each component fluid. A complexfluid can therefore be precisely, and without energy expenditure,separated into its component fluids and drawn to separate channels.

The separation specificity can be increased by a series of bifurcatingchannels. It should be understood that each directing channel plusbifurcating separating channels may be considered a “Y-discriminator.”In some embodiments, a series of Y-discriminators may be utilizedwherein a first Y-discriminator can separate a complex fluid intocomponent fluids A and B. Following component fluid B, anotherY-discriminator may be reached, which may separate fluid B into twocomponent fluids C and D, and so on. At each Y-discriminator the rangeof interfacial surface energies being separated may become smaller.Provided a sufficient number of Y-discriminators, a complex fluid can bereduced to pure component fluids.

A number of different embodiments can be imagined, some of which mayinvolve repeated series of Y-discriminators, or connecting one of theoutput channels back to the input channel for improved purity of thecomponent fluid output. However, for flow circuits, external power maybe required to maintain the flow. For example, a pulsed sonic driver maybe used to recirculate complex fluids.

Referring to FIG. 2 , a diagram schematically shows one embodimentwherein a single component fluid may be highly purified from a complexfluid. The microstructure discriminator 200 may include a base 202 onwhich directing channels 204 and separating channels 206 and 208 may bearranged in an array of Y-discriminators 210. Complex fluid 212 may bepumped 213 from reservoir 211 and may enter first directing channel 204.It may then be divided into component fluids 216 and 218 at bifurcation220. In some embodiments, component fluid 216 may be waste, and may bediscarded. Component fluid 218 may continue on to Y-discriminator 222and may be divided into components fluids 224 and 226. Component fluid224 may be returned to the input reservoir 211 via directing channel228. Component fluid 226 may then continue on to Y-discriminator 230 andmay be divided into fluid components 232 and 234. Component fluid 232may be returned to component fluid 218 via directing channel 236. Insome embodiments, this structure can be continued indefinitely,indicated by line 237. Final Y-discriminator 238 may divide complexfluid 240 into component fluids 242 and 244. Component fluid 244 may beemptied into collection reservoir 246. As fluid is collected inreservoir 246, diluent fluid (water) may be supplied by reservoir 248and added to reservoir 211 to compensate the fluid lost to reservoir246. A monitor 250 on separation channel 252 may be used to monitorfluid conductivity. When the fluid conductivity reaches a target valuethe separation process may be considered complete. The monitor may beany monitor relevant to the fluid separation process, such as an opacitymeter, a densitometer, or light scattering meter.

In addition to the above-mentioned embodiments, the complex fluid flowmay be aided by centrifugal force. Referring now to FIG. 3 , in someembodiment, a microstructured discriminator 300 may include a rotatableplane-circular platform 302 including a base 304. At the center 306 ofbase 304 may be located supply reservoir 308 which can be connected toradial directing channels 310; and separating channels 312 extendradially from the directing channels 310. Accordingly, Y-discriminators314 are arranged radially. The complex fluid 316 may be centrifugallydriven radially out of supply reservoir 308. Complex fluid 316 may becomprised of component fluids 318 and 320 and a carrier fluid, whereincomponent fluid 318 may have a specific weight that is less thancomponent fluid 320. Base 304 may have thickness 324. As is shown,Y-discriminators 314 may be arranged in radial direction 322 whereinseparating channel 328 may be higher than separating channel 326. At thebifurcation region 330 between the directing channel 310 and theseparating channels 326 and 328, the interfacial surface energy of theupper separating channel 328 may be greater than that of the lowerseparating channel 326. The surface energy of the component fluid 318may be greater than that of the surface energy of the component fluid320. Under the action of gravity and the surface energy of componentfluids 318 and 320, the upper separating channel 328 may attractcomponent fluid 318 and the lower separating channel 326 may attractcomponent fluid 320. Thereby, the component fluids of different surfaceenergies may be separated.

It should be appreciated these microstructured interfacial energies canbe developed in a three-phase environment. In a complex fluid comprisingtwo or more component fluids, at least one of these component fluids mayserve as the carrier phase in a specific interfacial geometry. Whichcomponent fluid acts as the carrier phase may be surface energydependent. However, in a fluid separating scenario it may be useful forthe complex fluid to be comprised of three component fluids wherein oneof the component fluids acts as the carrier phase for all interfacialstates in the microstructure discriminator. In some embodiments, wateris the carrier phase.

When a complex fluid contacts a microstructured surface one of thenon-carrier fluids may form the drop and the carrier fluid may surroundthe drop-surface interface. In a Y-discriminator containing the complexfluid comprising component fluids A, B and Carrier, the component fluidsA and B may form droplets in distinct separating channels of theY-discriminator. The droplet in each separating channel may form acontact angle with the microstructured surface. If the microstructuredsurface forms an interfacial energy gradient, then the radii of thecurvatures of both ends of the interfacial droplet may be asymmetricbecause of the distribution of surface energy gradient. This asymmetrymay be due to a spatial pressure differential relative to the carrierphase. The pressure differential drives a net pressure difference insidethe droplet, which may provide a directing force. Each separatingchannel maximizes the driving force for each of the component fluids Aand B, and component fluids A and B may select the separating channelwhere the driving forces is greatest.

In some embodiments, it is not necessary that both component fluids bepositively attracted to the separating channels, one separating channelmay serve simply as a drain. For example, if gravity (or centrifugalforce) is used to generally drive any fluid to the drain channel, then aseparating channel may be arranged higher in the gravitational fieldwith a high driving force for one of the component fluids and sufficientto overcome the gravitational field, which can act to separate onecomponent fluid from the other component fluid.

Referring to FIG. 4 , the detailed mechanism of a Y-discriminator 400 isillustrated. Y-discriminator 400 may include directing channel 402 andseparating channels 404 and 406. The lumenal surface of channel 402 maybe paved with microstructure 408, and the lumenal surfaces of separatingchannels 404 and 406 may be paved with microstructure 410 and 412,respectively. Microstructures 408, 410, 412 may generally be differentin composition and/or pattern. The bifurcation region 414 may act as acomponent fluid separating region where component fluid 416 separatesfrom component fluid 418. The microstructures of each channel may extendsome distance 420 inside the bifurcation region 414. Because thebifurcation region 414 may have a diameter greater than the directingchannel 402 the fluid speed may be caused to decrease. Thermal motionmay dominate the slower fluid speed, wherein component fluid 416 may beattracted to the region of separating channel 404 and component fluid418 may be attracted to the region of separating channel 406. Uponseparation, the surface energy gradients 422 may drive the componentfluids 416 and 418 down their respective separating channels.

As shown in FIG. 5 , surface textures 500 may create an interfacialsurface energy gradient for a directing channel as calculated usingLaplace's equation. Referring to FIG. 5 a , microstructures may bedisposed on a base 502. A hierarchical microstructure 503 comprisingsmall pillars 504 may be positioned on large pillars 506. The spacing508 between pillars may be scaled with their diameters. In someembodiments, the spacing 508 may be increasing between each adjacent setof microstructures. For example, spacing 508 may be less than spacing510. The spacing or the pitch 512, may be scaled. Referring to FIG. 5 b, the height 514 of pillars 506 may be sinusoidally varied, while thedimensions of pillars 504 may be held constant. The spacing 508 may alsobe held constant. Referring to FIG. 5 c , the spacing 508 or pitch 512may be decreased spatially. The dimensions of pillars 504 and 506 may beheld constant. For example, FIG. 5 c describes a pattern that may drivefluid in the direction 514.

The diameters of pillars 506 may be from 10 microns to 100 microns, thediameters of pillars 504 may be from 1 to 10 microns. The aspect ratios(height divided by diameter) may be in the range 0.1 to 10. Pitch canvary from 1 micron to 1000 microns, or more.

As shown in FIG. 6 , surface textures 600 may create an interfacialsurface energy gradient for a separating channel as calculated usingLaplace's equation. Surface texture 600 may be disposed on base 602.Base pillars 604 may include a first hierarchical level. Disposed onbase pillars 604 are fins 606. Fins 608 directly between adjacent basepillars 604 may bridge the space between the base pillars withoutdecreasing their height 610 to the base plane 602. Fins 606, 608 maycomprise a second hierarchical level. The base pillars 604 may beterminated with spheres 610 on which are disposed uniformly spaced smallpillars 612. Pillars 612 may include a third hierarchical level. Thespacing 614 between base pillars 604 may be decreasing. While notdepicted in FIG. 6 , the base pillars 604 may be disposed in atwo-dimensional rectangular array, and not as a one-dimensional array asdepicted. The distance 616 between fins 606 may decrease in thedirection 618 in relation to the base pillar 604. The fins 606 may beetched with microgrooves 620 which may generally be orthogonal to thefin axis.

As shown in FIG. 6 , in some embodiments, one of possibly many componentfluids may form a drop 622 on fins 606. The narrowing distance 616 inthe direction 618 may generate an interfacial energy gradient thatdrives drop 622 to the sphere 610. The smaller pillars 612 may thenconsolidate a plurality of drops 622. The consolidated drop 624 maymigrate around the sphere in the direction of the energy gradientcreated by adjacent base pillar 626 and its associated sphere 610. Thisenergy gradient may cause drop 624 to bridge the distance between thebase pillars (as shown). Pillar 626 may consolidate drops 624 to producedrop 628 which continues the transference and consolidation process.

In some embodiments, separation of two component fluids may not requirechanging the basic geometry of FIG. 6 . In some embodiments, a device600 as previously disclosed may be used but the materials comprisingdevice 600 can be changed. In this way, a microstructured discriminatorcan be constructed that operates for a wide range of complex fluidcompositions. In other embodiments, a specific application for a complexfluid such as the separation of red blood cells from whole blood may beused such that maximum performance is achieved by designing the devicefor both the composition and microstructure geometry. These calculationscan be carried out using Laplace's equation, and the range ofcomposition of the complex fluid. In some embodiments, the smallerpillars 612 can be replaced by circular coating patches of a calculatedinterfacial surface energy.

Referring now to FIG. 7 , the internal microstructure of a separatingchannel 700 of a microstructure discriminator for separating red bloodcells from whole blood is disclosed. It should be appreciated that redblood cells carry a high negative electric charge, and thus have highsurface energy, and may be attracted to hydrophilic microstructures.Microstructure 700 may be configured as a cylindrical channel byassociating edge 702 with 704. In the cylindrical configuration,microstructure edge 706 may join seamlessly with microstructure edge708. In the cylindrical configuration, microstructure 710 may form acontinuous ridge that spirals on the lumen of the formed cylinder. Thelength 712 may form one turn of the formed spiral. The distance 714between turns may decrease in direction 716. Distance 714 may be lessthan distance 718, and distance 718 may be less than distance 720. Thespiral pattern may form the first hierarchical level. At the top surfaceof ridge 710 may be a v-groove 722. Internal angle 724 may decrease inthe direction 716. Angle 724 may be greater than angle 726, and angle726 may be greater than angle 728. The initial internal angle 724 may beapproximately 180 degrees. The final internal groove angle (notpictured) is configured to be the contact equilibrium angle (minimumenergy state) of a red blood cell with the final internal groove angle.Groove 724 may include the second hierarchical level. Nano protuberances730 may cover the surface of groove 724. The protuberances 730 may beutilized to prevent fouling by protein deposition. Protuberances 730 mayform a third hierarchical level.

It should be appreciated that both groove 724 and winding spacing 714may form an interface energy gradient in the direction 716. Furthermore,inter-groove regions 732 may be hydrophobic with respect to grooveregions 724. The juxtaposition of 732 and 724 may form a Wenzel-Cassiestate, which may prevent the cells from clumping and occluding theseparating channel 700 of the microstructured discriminator. Inoperation, cells may be individually and orderly directed in a spiralpath in direction 716.

The second separating channel branch of the Y-discriminator of themicrostructured discriminator described above may be a negativelycharged, insulated tube with hydrophobic surface texture. When thecharge is used, the blood column must be grounded to the charge source.No current flows in the blood column.

Referring to FIG. 8 , the internal microstructure of a separatingchannel of a digital microstructure discriminator 800 is disclosed.Internal microstructure 800 may include an insulting base polymer 802,electrodes 804 embedded in base layer 802, electrical conduits 806,grounding electrode 808, and switching means 810. Switching means can beconfigured to be a closed circuit or an open circuit by an externalcontroller (not shown). Base layer 802 may be configured as atwo-dimensional sinusoidally varying surface 838 and may include thefirst hierarchy level. Cylinders 812 may comprise the second hierarchylevel. Smaller cylinders 814 may include the third hierarchy level.Large cylinders 812 may be configured with fins 816 projecting radiallyand joining seamlessly with ridges 818 disposed on base layer 802. Twofin-to-ridge-to-fin configurations are illustrated. In some embodiments,ridges 820 may join fins 822 and 824 on separate large cylinders 812. Insome embodiments, ridges 826 may join fins 828 reside on the same largecylinder 812. In both cases, the ridges 820 and 826 may be arrangedapproximately concentrically on the first hierarchy sinusoids 838.

The separator surface 800 may operate by first attracting a hydrophiliccomponent fluid to the third hierarchy level 814 in the powered offstate in which all switches 810 may be in the open state. In this firstinterfacial state, component fluid at position 830 may be hydrophilicrelative to carrier component fluid at position 832. These adjacenthydrophilic-hydrophobic interfaces may form a Wenzel-Cassie state. Itshould be appreciated that in the unpowered state, surface 814 may behydrophilic relative to intra-cylinder surface 836.

In the powered state, charge from charge source 839 may be delivered toone or more electrodes 804. In some embodiments, all the electrodes canbe turned on at once, or may be turned on in a sequence, which may causecomponent fluid at position 830 to move in direction 842. With referenceto the component fluid at position 830, when switch 840 is closed(turned on), the base layer 802 may become locally charged. As aconsequence of this charge, intra-cylinder surface 836 may become morehydrophilic relative to 814.

This phenomenon is known as electrowetting. The sign of the chargedelivered to electrodes 804 may depend on the composition of the complexfluid to be separated. Electrowetting may cause hydrophilic componentfluid residing at position 830 to displace carrier component fluidresiding at position 832, such that the hydrophilic component may nowreside at position 832 and carrier component fluid may now reside atposition 830. The action of electrowetting is to advance the hydrophiliccomponent fluid in direction 842. Subsequently, switch 840 may be opened(turned off), location 834 may become more hydrophilic than position832, and hydrophilic component fluid may advance to position 834. Whensurfaces 814 are loaded with hydrophilic component fluid, turning allelectrodes on simultaneously may cause Wenzel-Cassie isolatedhydrophilic component fluids to advance in direction 842.

In some embodiments, an energy gradient can be obtained by selection ofmaterial, spacing of microstructures, or grading the charge delivered toeach electrode 804, such that those electrodes 804 farthest in direction842 may be most charged, and those electrodes 805 proximal in direction842 may be least charged. This situation may be achieved by varying thecapacitance 844 at each electrode location. The flow may be reversed byreversing the charge gradient. Hence, the operation of separatingsurface 800 may be digital in the sense that discrete volumes ofhydrophilic component 830 may be separate and delivered discretely. Ifboth the switching means 810 and the capacitance means 844 areindividually controllable, then a wide variety of transportationsequences can be imagined. For example, fluid from both ends may beaccumulated in the center of a separating channel. It should beappreciated the above described digital aspect may be amenable to bothdirecting and separating channels.

Referring to FIG. 9 , a diagram of the evolution chamber architecture ofa landscape microstructured fluid discrimination device 900 for studyingcell-surface interactions is disclosed. The landscape microstructuredfluid discrimination device 900 may include an input directing channel902 and separating channels 904 and 906. The purpose of the separatingchannels may be to give the introduced organism a choice of textures onwhich to migrate. The choice may occur in the bifurcation region 908.The separating channels 904 and 906 may each lead to a differenttextured environment 910 and 912, respectively. Each texturedenvironment 910 and 912 may be surrounded by a smooth migration path914, which may act as a neural pathway for cells to choose betweenpropagating on the textured environment or continuing on to the nexttextured environment. Directing channels 916 and 918 may lead tobifurcation region 920 where additional landscape textures 922, 924,926, and 928 may be presented. The choice can be refinements on a designpresented in the previous landscape chamber. For example, landscapes 930and 932 can be variations on the theme presented in 910, and landscapes934 and 936 can be variations on the theme presented in 912. Landscapescan be repeated in the various arms to cover all combinatorialpossibilities. Multiple organisms may be introduced in the landscapemicrostructured fluid discrimination device 900.

Referring to FIG. 10 , a first embodiment of a fan discriminator forseparating red blood cells from whole blood according to the presentinvention is disclosed. Fan discriminator 1000 may include radiatingridges 1002 with pitch 1004 and amplitude 1006. The pitch 1004 mayincrease in radial direction 1008. Ridges 1002 may undulate in theradial direction 1008 with pitch 1010. Pitch 1010 may decrease in radialdirection 1008. Ridges 1002 may be populated with microstructures 1016which may include cylinder 1012 disposed on cylinder 1014. Continuousundulating ridges 1002 may be discretized by replacing the continuousstructure with cylindrical pillars varying in height according todiscrete positions on ridges 1002. The cylinder on cylinder structures1016 may be replaced by fins on the sides of discretizing pillars.

Blood cells 1018 may enter in port 1020 comprising pathways 1022entering along ridges 1002. Structures 1016 may generate structuredwater zones 1024 which may exclude particles such as red blood cells1018 but allow blood serum 1026 to pass. Varying pitch 1010 may create asurface energy gradient that creates flow 1028. Flow 1028 may createport flow 1030. Flow 1030 may cause red blood cells 1018 to exit alongpathways 1022.

It should be appreciated that differential surface energy structures canbe created by changes in pitch (as given in 1000), amplitude, andchemically altering the surface.

Those embodiments described above are provided to clarify the presentinvention to enable the persons skilled in the art to understand, makeand use the present invention. However, it is not intended to limit thescope of the present invention, and any equivalent modification andvariation according to the spirit of the present invention is to be alsoincluded within the scope of the present invention.

Thus, although there have been described particular embodiments of thepresent invention of a new and useful Microstructured DiscriminationDevice it is not intended that such references be construed aslimitations upon the scope of this invention except as set forth in thefollowing claims.

1. A fluid separating device comprising: at least one directing channelhaving a first end and a second end, the second end being in fluidcommunication with a plurality of separation channels, and at least oneof the plurality of separation channels including a surface comprising ahierarchical microstructure configured to selectively direct flow of afluid.
 2. The fluid separating device of claim 1, further comprising aninjection port in fluid communication with the first end of the at leastone directing channel.
 3. The fluid separating device of claim 1,wherein the hierarchical microstructure of at least one of the pluralityof separation channels provides a graded Wenzel state.
 4. The fluidseparating device of claim 1, wherein the hierarchical microstructureprovides a graded Cassie state.
 5. The fluid separating device of claim1, wherein the directing channel includes a surface comprising ahierarchical microstructure configured to direct flow of a fluid fromthe first end to the second end.
 6. The fluid separating device of claim1, wherein the plurality of separation channels further comprises atleast first and second separation channels; the first and the secondseparation channels each including a surface comprising a hierarchicalmicrostructure configured to selectively direct flow of a fluid.
 7. Thefluid separating device of claim 6, wherein the first separationchannel's hierarchical microstructure and the second separationchannel's hierarchical microstructure each comprises distinct surfaceenergy gradients.
 8. The fluid separating device of claim 7, wherein thefirst separation channel's hierarchical microstructure and the secondseparation channel's hierarchical microstructure each comprises adifferent spatial periodicity.
 9. The fluid separating device of claim7, wherein the distinct surface energy gradient of the first separationchannel's hierarchical microstructure is configured to separatecomponents of the fluid into distinct flows.
 10. The fluid separatingdevice of claim 7, wherein the distinct surface energy gradient of thesecond separation channel's hierarchical microstructure is configured toseparate components of the fluid into distinct flows.
 11. The fluidseparating device of claim 1, wherein the hierarchical microstructurefurther comprises spatially varying microstructure components, whereinthe spatially varying microstructure components are arranged in ahierarchy and vary in height between 10 nanometers and 1000 microns. 12.The fluid separating device of claim 1, wherein the hierarchicalmicrostructure further comprises spatially varying microstructurecomponents, wherein the spatially varying microstructure components arearranged in a hierarchy and vary in diameter between 10 nanometers and1000 microns.
 13. The fluid separating device of claim 1, wherein thehierarchical microstructure further comprises spatially varymicrostructure components, wherein the spatially varying microstructurecomponents have a pitch of between 10 nanometers and 1000 microns. 14.The fluid separating device of claim 7, wherein the first separationchannel is configured to direct a first solid component of the fluidalong the first separation channel, the second separation channel isconfigured to direct a second solid component of the fluid along thesecond separation channel, and wherein the first solid component isdifferent from the second solid component.
 15. The fluid separatingdevice of claim 14, wherein the first solid component comprises redblood cells and the second solid component comprises platelets.
 16. Thefluid separating device of claim 1, further comprising at least onecollection reservoir that is fluidly communicated with at least one ofthe plurality of separation channels.
 17. A fluid separating devicecomprising: at least one directing channel having a first end and asecond end, the second end being in fluid communication with a pluralityof separation channels; at least one of the plurality of separationchannels including a surface comprising a hierarchical microstructureconfigured to selectively direct flow of a fluid; and at least one ofthe plurality of separation channels diverging with a first output beingin fluid communication with a return line and a second output being influid communication with a collection reservoir.
 18. The fluidseparating device of claim 17, further comprising an input reservoir forsupplying a fluid.
 19. The fluid separating device of claim 18, furthercomprising an input port configured to receive fluid from the inputreservoir and direct the fluid to the directing channel.
 20. The fluidseparating device of claim 17, wherein the return line is in fluidcommunication with the input reservoir. 21.-28. (canceled)